Mechanical and electrical actions of cardioactive steroids will be studied in isolated canine false tendons (Purkinje tissue) and ventricular trabeculae, and in the exposed hearts of anesthetized dogs. Electrical effects to be studied are related to the transient depolarizations (also called low amplitude potentials) induced by low concentrations of digitalis. We shall examine phasic alterations of excitability, speed of depolarization, membrane potential, and conduction velocity, together with the actions of other agents which initiate or modify transient depolarizations (stretch, ionic composition, other drugs). After-contractions will be studied in relation to the coincident depolarizations; and the relation of after-contractions to the inotropic action of the drug will be studied. Counterparts of these electrical and mechanical effects will be sought in the intact heart. We expect to find rate-dependent phasic alterations in intraventricular conduction velocity and in subendocardial excitability in the intact heart at an early stage of digitalis toxicity. Curves of restitution of contractility after the last of a train of driven pulses should reveal the presence of aftercontractions. The possible cause of seasonal variations in the behavior of isolated preparations and in their response to digitalis will be studied in both isolated and intact heart preparations.